The ability to deliver DNA to target cells has been playing a key role in the development of new approaches, such as gene therapy and DNA vaccination, for treating and controlling diseases. DNA delivery systems have been classified as viral and non-viral vector systems. Although viral vectors are highly efficient at delivering DNA into cells, their routine uses in clinic and basic research laboratories have been limited because of, inter alia, their high toxicity, restricted targeting of cells, limited DNA carrying capacity, production and packaging problems, recombination, and high cost.
Non-viral vectors, the majority of which are synthetic gene carrier systems, have advantages in terms of simplicity of use, ease of large-scale production, and lack of specific immune response.
The use of polymers for carriage of DNA carrier is a promising non-viral gene delivery approach, most of which is composed of cationic polymer segments that form a condensed complex with DNA to protect DNA against digestion by enzymes. The condensed polymer-DNA complex also packs into compact and small nano-particles, which can be internalized by cells through endocytosis process and transferred through the diverse barriers toward the nucleus of the target cell, where the gene can be expressed.
Cationic polymers of linear, branched, star and dendritic structures have been studied as DNA condensation agents in the context of non-viral gene delivery. Controlled chemical synthesis of cationic polymers ensures that the size and shape of the polymers are consistent and defined, thereby improving the reproducibility of NDA delivery. Polyethyleneimine (PEI) is one of the most frequently studied polycations for this application. The size and the structure of PEI have strongly influenced the efficiency of gene transfer technologies with regard to transfection activity and cytotoxicity. Generally, low molecular weight branched PEI (≦2000 Da) proved to be nontoxic but displayed very poor transfection activity. By contrast, high molecular weight branched PEI (≦25 kDa) showed high transgene expression but also significant cytotoxicity. In the intermediate molecular weight range (2000-25 kDa), the PEI is of medium to low cytotoxicity and also medium transfection activity. Furthermore, no matter what the molecular weight is or whether the cationic polymers are linear, branched, star, or dendrimers, they are mostly non-biodegradable, which may cause sustained damage for the cells after the gene delivery.
There is a need to provide polycations that overcome or at least ameliorate one or more of the disadvantages described above.